chr15-27983498-G-A

Variant names:

• chr15-27983498-G-A
• rs12910433
• NM_000275.3:c.1365-15C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):​c.1365-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,612,918 control chromosomes in the GnomAD database, including 345,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23976 hom., cov: 32)
  • Exomes 𝑓: 0.64 (321523 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0380
• Publications: 21 publications found

Genes affected

OCA2 (HGNC:8101): (OCA2 melanosomal transmembrane protein) This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

OCA2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-27983498-G-A is Benign according to our data. Variant chr15-27983498-G-A is described in ClinVar as Benign. ClinVar VariationId is 255720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1365-15C>T		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.1293-15C>T		intron	N/A	NP_001287913.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1365-15C>T		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.1293-15C>T		intron	N/A	ENSP00000261276.8
	OCA2	ENST00000910120.1		c.1365-15C>T		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76875 AN: 151970 Hom.: 23984 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.511

GnomAD2 exomes AF: 0.541 AC: 136088 AN: 251344 AF XY: 0.547

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.714

Gnomad OTH exome AF: 0.594

GnomAD4 exome AF: 0.644 AC: 941109 AN: 1460830 Hom.: 321523 Cov.: 41 AF XY: 0.638 AC XY: 463606 AN XY: 726796

African (AFR) AF: 0.167 AC: 5586 AN: 33458

American (AMR) AF: 0.381 AC: 17028 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 15564 AN: 26128

East Asian (EAS) AF: 0.116 AC: 4612 AN: 39698

South Asian (SAS) AF: 0.365 AC: 31495 AN: 86230

European-Finnish (FIN) AF: 0.743 AC: 39650 AN: 53398

Middle Eastern (MID) AF: 0.583 AC: 3362 AN: 5764

European-Non Finnish (NFE) AF: 0.709 AC: 787827 AN: 1111066

Other (OTH) AF: 0.596 AC: 35985 AN: 60368

GnomAD4 genome AF: 0.505 AC: 76857 AN: 152088 Hom.: 23976 Cov.: 32 AF XY: 0.500 AC XY: 37181 AN XY: 74356

African (AFR) AF: 0.185 AC: 7659 AN: 41470

American (AMR) AF: 0.428 AC: 6532 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2063 AN: 3472

East Asian (EAS) AF: 0.147 AC: 759 AN: 5166

South Asian (SAS) AF: 0.346 AC: 1665 AN: 4812

European-Finnish (FIN) AF: 0.743 AC: 7870 AN: 10592

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48374 AN: 67978

Other (OTH) AF: 0.508 AC: 1074 AN: 2114

Alfa AF: 0.629 Hom.: 19827

Bravo AF: 0.472

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Tyrosinase-positive oculocutaneous albinism (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.50
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12910433; hg19: chr15-28228644; COSMIC: COSV62344987;